Pyrrolo quinolones

Witkop and Goodwyn reported (288) that ozonolysis of yohimbine (74) and its derivatives led to the corresponding quinolone derivatives. This reaction has been thoroughly investigated by Winterfeldt (289). For example, autooxidation of lactam 347 resulted in quinolone 599, which upon treatment with phosphoryl chloride, followed by catalytic reduction, gave pyrrolo[3,4-h]quioline derivative 600 (290). This transformation was also used as a key step in the biomimetic synthesis of camptothecin (601), performed by Winterfeldt et al. (291, 292). 

A closely related reaction between 1 -arylpyrrolidine-2-thiones 96 and diethyl bromoma-lonate97 under Reformatsky conditions afforded l-arylpyrrolidin-2-ylidenemalonates 98, which, upon polyphosphoric acid (PPA) induced cyclization, opened a route to pyrrolo[l, 2-a] quinolones 99145, tricyclic analogues of quinolone antibiotics (equation 58). 

Baylis-Hillman adducts such as 55 and 56 derived from 2-nitrobenzaldehydes were shown to function as useful precursors to functionalized (1H)-quinol-2-ones and quinolines. Treatment of 55 and 56 with iron and acetic acid at 110 °C afforded 57 and 58, respectively <02T3693>. A variety of other cyclization reactions utilized in the preparation of the quinoline scaffold were also reported. An iridium-catalyzed oxidative cyclization of 3-(2-aminophenyl)propanols afforded 1,2,3,4-tetrahydroquinolines <02OL2691>. The intramolecular cyclization of aryl radicals to prepare pyrrolo[3,2-c]quinolines was studied <02T1453>. Additionally, photocyclization reactions of /rans-o-aminocinnamoyl derivatives were reported to provide 2-quinolones and quinolines <02JHC61>. Enolizable quinone and mono- and diimide intermediates were shown to provide quinolines via a thermal 6jt-electrocyclization <02OL4265>. Quinoline derivatives were also prepared from nitrogen-tethered 2-methoxyphenols. The corresponding 2-methoxyphenols were subjected to a iodine(III)-mediated acetoxylation which was followed by an intramolecular Michael addition to afford the quinoline OAc O... 

All of the quinolones with an S,S-2,8-diazabicydo[4.3.0]non-8-yl radical (CAS 4aS-CTs-octahydro-pyrrolo[3.4-b]pyridine) synthesized by us proved to be more effective than the corresponding active compounds with an i ,i -2>8-diazabicyclo[4.3.0 non-8-yl substituent. Some examples of these compounds are shown in Tab. 14.5. 

During their early investigations of harmine, Perkin and Robinson attempted a synthesis of what they thought to be isoharman. The 2-quinolone amide (74) was cyclized with phosphoryl chloride to a chloro compound (75), which gave 2.ff-pyrrolo[2,3-6]quinoline (76, R = H) with tin and hydrochloric acid, and its 3-methyl derivative (75, R = Me) with methylmagnesium iodide. The name quinindole ... 

A Parham cyclization strategy has been used to synthesize a wide variety of isoquinolines. For example, iodide 66 is smoothly converted to 67, which can be reduced (sodium borohydride/trifluoroacetic acid, 99%) or treated with nucleophiles and a Lewis acid to effect a-amidoalkylation. Likewise, imidazo[4,3-a]isoquinolinones (68), ° thiazolo[4,3-a]isoquinolinones (69), ° pyrrolo[2,l-a]isoquinolines (70), pyrrolo[ 1,2-6] isoquinolines (71), pyrrolo[l,2-6]acridinones (72), ° pyirolo[l,2-g]quinolones (73), ° thieno[3,2-y]indolizinones (74), ° and furo[3,2-/lindolizinones (75). ° It should be noted that the latter ring system 63 was prepared by deprotonation (LDA) rather than halogen-lithium exchange. °... 

The reaction of terminal alkynes RC=CH (R = aryl, alkyl) with iodine, TSNHNH2, and Bu OOH has been found to afford ( )- -iodovinyl sulfones ArC(I)=CHTs. lodination of A -(alkynoyl)-6-methoxytetrahydroquinolines (21) has been found to trigger an intramolecular ipso-attack of the primary intermediate on the electron-rich aromatic ring, resulting in the formation of pyrrolo-[2,l-/ quinolones (22) (R = aryl, heteroaryl, vinyl, alkyl). ... 

Pyrrolo[2,l-a]isoquinoline derivatives (27) were synthesized using Cgo-Bodipy dyads (28) as excellent photosensitizers (Scheme 13)/ Direct irradiation of glycine methyl ester to Ceo afforded [3 - - 2] cycloadduct/ Akasaka and his coworkers found the photocycloaddition of 2-ada-mantane-2,3-[3ff]diazirine and disilyliranes to Cso-metallofullerenes/ Intra- and inter-molecular photocycloaddition of alkenes to coumarin, quinolone, and isoquinolone derivatives have been reported by several groups. Griesbeck et al. found that the intramolecular photocycloaddition of cyclohexene moiety to coumarin (29) was catalysed by molecular ojygen. [2 + 2] Photocross dimer (33) of coumarin derivative (31) and 5-fluorouracil derivative (32) was obtained by laser irradiation/ Bach reported enantioselective intramolecular photocycloaddition of coumarins (34) to alkenes catalysed by a chiral Lewis acid (36) (Scheme 14)/ ... 

Quinolones by migration of carbon-carbon double bonds-quinolines s. lA, 749 -Pyrrolo[3,2,l-ij]-... 

Further studies with P. citrinum VKM FW-800 obtained from the permafrost region of Northern Russia, led to the isolation of the alkaloids (+)-quinocitrinine A and (—)-quinocitrinine B, which are diastereomers at the C-1 and C-9 stereocenters (186). These alkaloids were the first pyrrolo[3,4-lr]quinoline-type representatives isolated from microbial sources. Their structures are unique in that a quinolone skeleton is conjugated with a y-lactam ring. A biomimetic total S3mthesis of quinolactacin B was reported by Tatsuta s group (215). A new enantioselective synthesis of quinolactacins A2 and B, via the skeletal rearrangement of a p-carboline to the pyrrolo[3,4- ]quinolin-4(lf-D-one system by an... 

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